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Genomic Profiling of the Steroidogenic Acute Regulatory Protein in Breast Cancer: In Silico Assessments and a Mechanistic Perspective

1
Departments of Immunology and Molecular Microbiology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
2
Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
3
Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
4
Physiologie de l’axe gonadotrope U1133, Institut National de la Santé et de la Recherche Médicale, CNRS, Biologie Fonctionnelle et Adaptative UMR 8251, Université Paris Diderot, 75205 Paris, France
5
Department of Dermatology and Laboratory Medicine, Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL 35294, USA
6
Veterans Administration Medical Center, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 623; https://doi.org/10.3390/cancers11050623
Received: 18 April 2019 / Revised: 27 April 2019 / Accepted: 30 April 2019 / Published: 4 May 2019
(This article belongs to the Special Issue Application of Bioinformatics in Cancers)
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Abstract

Cancer is a multifactorial condition with aberrant growth of cells. A substantial number of cancers, breast in particular, are hormone sensitive and evolve due to malfunction in the steroidogenic machinery. Breast cancer, one of the most prevalent form of cancers in women, is primarily stimulated by estrogens. Steroid hormones are made from cholesterol, and regulation of steroid/estrogen biosynthesis is essentially influenced by the steroidogenic acute regulatory (StAR) protein. Although the impact of StAR in breast cancer remains a mystery, we recently reported that StAR protein is abundantly expressed in hormone sensitive breast cancer, but not in its non-cancerous counterpart. Herein, we analyzed genomic profiles, hormone receptor expression, mutation, and survival for StAR and steroidogenic enzyme genes in a variety of hormone sensitive cancers. These profiles were specifically assessed in breast cancer, exploiting The Cancer Genome Atlas (TCGA) datasets. Whereas StAR and key steroidogenic enzyme genes evaluated (CYP11A1, HSD3B, CYP17A1, CYP19A1, and HSD17B) were altered to varying levels in these hormone responsive cancers, amplification of the StAR gene was correlated with poor overall survival of patients afflicted with breast cancer. Amplification of the StAR gene and its correlation to survival was also verified in a number of breast cancer studies. Additionally, TCGA breast cancer tumors associated with aberrant high expression of StAR mRNA were found to be an unfavorable risk factor for survival of patients with breast cancer. Further analyses of tumors, nodal status, and metastases of breast cancer tumors expressing StAR mRNA displayed cancer deaths in stage specific manners. The majority of these tumors were found to express estrogen and progesterone receptors, signifying a link between StAR and luminal subtype breast cancer. Collectively, analyses of genomic and molecular profiles of key steroidogenic factors provide novel insights that StAR plays an important role in the biologic behavior and/or pathogenesis of hormone sensitive breast cancer. View Full-Text
Keywords: hormone sensitive cancers; breast cancer; StAR; estrogen; steroidogenic enzymes hormone sensitive cancers; breast cancer; StAR; estrogen; steroidogenic enzymes
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Manna, P.R.; Ahmed, A.U.; Yang, S.; Narasimhan, M.; Cohen-Tannoudji, J.; Slominski, A.T.; Pruitt, K. Genomic Profiling of the Steroidogenic Acute Regulatory Protein in Breast Cancer: In Silico Assessments and a Mechanistic Perspective. Cancers 2019, 11, 623.

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